Practical aspects of cytokine therapy

Biological therapy with cytokines and growth factors represents a completely new approach in cancer therapy and forces us to adapt our research procedures originally tailored to cytotoxic agents. The lack of reliable predictive in vitro systems or animal models for biological agents and the fact that promising candidates must proceed rapidly to the clinic implies that a drug's therapeutic potential can only be assessed following careful studies in man. Consequently, the effectiveness of clinical trials must be improved by closely relating them to research programs utilizing material from cytokine-treated patients. In clinical practice, patients with low tumor burden may profit most from therapy with immunomodulators, which requires minimally effective doses rather than maximally tolerated dosages. Hemopoiesis can be influenced either by hemopoietic growth factors or by negative regulators, which may prevent stem cell damage during chemotherapy. According to the principles of autocrine growth mechanisms, resting malignant cells may be triggered into cell cycle by their growth factor(s), thus becoming more sensitive to chemotherapy. When discussing the fascinating aspects of the cytokine network, we must be aware that we are only beginning to understand the mechanisms of biological therapy and that close cooperation among preclinical and clinical scientists is required for its rational development.